I've watched most of them as well, and Irreversible was the worst for me, somehow, even though its subject matter isn't really as bad as some of the others.

The way too long and hyper realistic R scene is definitely a big part of it, but the movie also assaults you subconsciously throughout the whole thing. The soundtrack is full of low frequencies that are known to give people nausea and anxiety, and the constant strobe lights also just make it hard to even sit through the quiet scenes.

It is a punishing watch. Wouldn't want to watch it again.