For an overveiw on what routes best to/fro UK(which you have to pass anyway from that green Emerald island-unless using the direct ferry to FR): seat61,com

Now the not so nice part: all the time we have to bluntly tell new posters here that using a pass in ESpana is-a PITA. It is by far the worst country-about any tren must be RES and this wil cost, not that much, but can only effectively be done whilst in that country at a counter. With a fair chance on disappointment- tren completo-or that they will tell you. Plus that the network is mostly centered to lines to MAD in the centre-the once existing but even then not that good lines along the coast are partly gone.

Worst #2 is FRance-same RES problem for its fast TGV, though with patience and smart planning these can often be replaced by using slower local TER trains. And #3 ITaly-here it applies mostly to its longer distance hi-speed and IC treni-but with some planning this is doable. DO be aware that its quite a long trek from the north - MIlano to Sicilia (nearly 20 hrs, can do in a through sleeper=vagone letti) and you have to come back same way. Coming of ESpana-sur till Sicilia will take many, many hrs of sitting in treni. And from Sicilia to Puglia is-well, also quite a trek eating many hrs of sitting in treni that often are cancelled too.

I myself always hesitate very much in telling ::visit this/that if people do not even give the slightest hint on what they are interested in-and the usual nr 1-2-3 touristic sites can be found in any guidebook or site. Perhaps older Irish still are also interested in the various R-C religious places that are found in profound nrs in all these countries? But general touristy advice is better done on such forums as tripadvisor - common Qs anyone start asking are already there in multiple.

With only broad indications like "the south of France" and "the south of Spain" it's a bit difficult too give concrete advice, tips and tricks. :)

Anyway, are you adamant on the order of your destinations?

Perhaps it's more easy to ferry yourselves down directly to France from Ireland to Cherbourg or Roscoff, than gradually working your way to the south of France.

Slowly travel down to south Spain, and after that take a ferry from Barcelona to Cittavecchia (close to Rome) to venture into the south of Italy. Bypassing the relatively long, and slow only land road. (Although it has a lot of Nice destinations there) 

From there, up towards the alps, back to Paris or Brussels to get the Eurostar and do the UK.

Or Alternatively, Ireland - UK, find yourself a ferry that takes foot pax to Spain (Bilbao or Santander), usually from Portsmouth or Southampton.

Anyway, plenty of options, plenty of time and the western half of Europe ready to discovee. So a lot is possible. If you get a bit more concrete and what you'lld like to visit, and what you'lld rather skip, sure the community can get you some proper itinerary suggestions. 

Beware of april (Easter) in Spain and the semana santa, probably leading to many fully booked Spanish AVE's and other trains. 

Unsure where you plan in Sicily or what level of budget but assuming either Palermo or Syracuse (the 2 sides of Sicily at the end of the main train lines).

We stayed in a small B&B near the station in Palermo but there are many hotels of all grades - check out booking.com.
In Syracuse you need to stay in Ortigia (the heritage part of Syracuse) which is about a 20 to 30 min walk - do not take a taxi - 20 euro for less than 1,5 km. We stayed in an apartment with stunning views (again from Booking ,com - other sites are available). The apt was Casa Alfeo, but the bed is on a mezzanine with steep narrow steps. Otherwise superb and reasonable price.
 

Definitely avoid Spain during Semana Santa - last year I had problems booking tickets. And you do have to be there in person to get the reservations - bu there are slower routes. If you have time, do take FEVE line across the north of Spain from Santander to Ferrol.

And yes, the ferry from Barcelona to Italy is a good option but if you want to visit friends in the south of France,  there are ferries from Toulon and Nice to Corsica/Sardinia, trains  south, eg  in Sardinia get the train south to Cagliari and then another ferry across to Palermo.  I’m not sure if those ferry lines give Interrail and Eurail pass holders a discount.

There are ferries from Plymouth and Portsmouth to Santander and Bilbao (and from Roscoff to Bilbao) which depending on dates do take foot passengers. All operated by Brittany Ferries which afaik does not offer discount for Interrail passholders. Otherwise there are roughly two routes from Paris to Spain, after getting to Paris by Eurostar (book on time, limited passholder seats!):

• Paris-Hendaye on TGV (reservation €10-20), San Sebastián-Madrid (reservation €6.50-10). You'll probably need to cross the border on Euskotren (€2.75). Not possible in a day, so you'll have to stop somewhere (San Sebastián is nice, and famous for its pintxos).
• Paris-Barcelona TGV (2 daily, €35 reservation), and then onwards from Barcelona to wherever you want to go (direct trains to Seville, Córdoba, Málaga, Valencia, Alicante, Murcia, ... the once daily torre del Oro to Cádiz might also be interesting but it's slow). If you haven't spent a night in Paris, you probably need to spend one in Barcelona.

The book Europe by Rail has suggested routes and stopovers. Latest edition is the 17th. 
https://www.europebyrail.eu/

and of course Man in Seat 61 has routes such as London to Spain

https://www.seat61.com/Spain.htm