Meaning: What’s gotten into you? What’s the matter with you?
Literal translation: Which fly bit you?
Notes: The French expression quelle mouche t’a piqué ? (or quelle mouche te pique ?) reminds me of the rather vulgar English expression « what (bug) crawled up your butt (and died)? » but the French expression is only informal. It’s basically asking what’s up? why are you getting mad for no apparent reason? In terms of register, the more accurate English translations are expressions like « what’s the matter with you?, what’s gotten into you?, what’s eating you? »
Example:
C’est la troisième fois que tu as crié… quelle mouche t’a piqué ?
That’s the third time you’ve yelled… what’s gotten into you?
Mon École-French School 