Good luck with starting treatment, Dutch. The first couple of weeks won't be so bad. I can't say for certain how it should work, but I can tell you what I did. I didn't even wait two hours. It soothed my skin to put the aquaphor on right after application of the efudex. It doesn't appear to have stopped my face from being properly attacked by the medication. The efudex seemed to absorb into the skin immediately, and I don't think you'd want to try to wash it off. I'm guessing that a petroleum jelly based product, such as aquaphor, will simply seal in the medication and let it do its job.
BTW, I'm looking sooooo much better only one week after stopping treatment. I have limited red spots since most are turning more pinkish already. Some say I already look younger ;).