The visitors went behind to an early Sergio Canales penalty and then slipped 2-1 down when Nabil Fekir struck after Frenkie de Jong’s equaliser.
Sergio Busquets made it 2-2 on the stroke of half-time with a rare goal before Clement Lenglet headed the winner in the second half.
Both teams ended the game with 10 men after Fekir and Lenglet saw red, but Setien was impressed with his team’s performance and result after their Copa del Rey exit at Athletic Bilbao on Thursday.
“We have had two demanding games and have had to work very hard. Betis played very well in the first half and made it difficult to play out from the back
“We’ve tried to press too, but they have a lot of high quality players, Fekir played an extraordinary game and they made it complicated for us. We had our moments, we went for the game and I think we dominated the second half.
“I think you have to value our performance highly. Thursday was really difficult. We played well then and this has been similar.
“There are things we can improve, but I’m very happy with our attitude, we’ve come from behind twice tonight and you have to value the control we’ve had.”
It’s a big away win for Barcelona, particularly after their midweek disappointment, and sees them stay three points behind Real Madrid in La Liga. Barca now have two La Liga home games in a row, against Getafe and Eibar, and then head to Napoli in the Champions League.