So, making a mathematically wrong play, will always be -EV right?
depends on what you call a mathemically wrong play.

Lets say on the turn the pot is 100, villian bet 40 into the pot, you have a flush draw ~18% to hit. but you assume that if you hit then 50% of the time you will destack the villian of his remaining 500.

Pot odds wise you need to put 40 into a 140 pot 40/140=.28 > .18
so from a str8 pot odds approach you should not call.

but your expected value is .82*0 + .09*140 + .09*540 = 61.2 so you should call