possiblyI have high hopes the Flood will come back probably not because they were destroyedI desperately want to say no. The first Halo trilogy was all about fighting and destroying this unstoppable galactic nightmare which destroyed the Forerunners, the Flood. We finished that fight. We destroyed the Gravemind at the Ark. Yeah, there are more Flood spore out there on the other Halos and possibly other Forerunner laboratories, but having the Flood as another main enemy in ANOTHER trilogy of games would be somewhat redundant I think. I mean the Flood is an AWESOME, nightmarish enemy. But three games fighting them was enough. I don't want to fight them for ANOTHER three games. A new galactic threat is needed and will hopefully be fought in Halo 4.
TECHNICALLY, it's possible, because the flood came from another galaxy, and more could possibly come. But I agree, the creators would have to be pretty stupid to put them in another three games.