Deadpool himself, Ryan Reynolds has expressed interest in a crossover between Deadpool and the Avengers. Though both are a part of the Marvel family, Deadpool is not included in the Marvel Cinematic Universe and is owned by Fox, thus being separated on the big screen, save for references and jokes courtesy of Deadpool. The mutants and Deadpool all belong to Fox, but could we possibly see a deal like Sony made with the MCU for Spider-Man: Homecoming? It would happen if Ryan Reynolds has anything to say about it, no matter how expensive it would be to make.
"That sounds like a great idea but a very expensive idea. Can you imagine the shit-talking contest with Iron Man? Oh, that would be great. But it would have to be rated R to completely unharness everybody. Unbridle the merriment and watch them go..."
An R-rated version of the Avengers joined by Deadpool could be a pretty awesome spin-off, but it is doubtful that it will happen on the big screen. Maybe Reynolds can make it happen while hosting Saturday Night Live for a skit, but the big screen does not seem like an option.
Marvel's Kevin Feige has promised the end of the MCU as we know it with by the end of Avengers 4, so you never know, maybe Wade Wilson will join forces with the cast of what's left of the Avengers following the epic battle with Thanos, a battle that is so epic that it will be spread across two movies. It seems highly improbable that we would see Josh Brolin as Cable and Thanos in the same movie or even crossing streams for that matter, but Wade Wilson is another story all together.
Another point that Ryan Reynolds brought up was the cost of a movie that would contain them all. Sony's deal with the MCU had slightly less leverage as this was to be a reboot for the Spider-Man universe, but Deadpool was an out of left field box office success, which would mean a lot more leverage on Fox's part. But that's not to totally crush the dreams of the crossover ever happening because anything is possible, but this just seems highly improbable and next to impossible.
So, we'll probably never see a big screen crossover between the Avengers and Deadpool, but there's still going to be more movies by the MCU and Fox, so maybe we can see some partial crossovers in the future. Wade Reynolds trading insults with Drak the Destroyer and Rocket could be a winning combination as could Deadpool and Iron Man. Avengers: Infinity War should prove that things that were once thought to be impossible can actually end up happening. In the meantime, Deadpool 2 is currently in production while Avengers: Infinity War has wrapped filming and Avengers 4 has just started principal photography. There are a lot of different versions of the Marvel universe coming our way.