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It wouldn't be hard on Mewtwo even at that, because he could just set up a few barriers to mitigate his punches and disable Doflamingo, and there's the fact that he can use recover.CinCameron20 said:-snipped-
Doflamingo's attacks would be strong enough to cause severe damage to Mewtwo if they hit, but I believe that his threads would fall prey to Mewtwo's telekenetic powers.
Mewtwo wins mid-difficulty.