Matthias Ginter, Vincenzo Grifo and Yuito Suzuki all chipped in with a goal and an assist for Julian Schuster's side, which will face LaLiga side Celta Vigo in the last eight. 

It took just 19 minutes for Freiburg to open the scoring through Ginter, who flicked Grifo's teasing free-kick from the left past Tobias Lawal and in off the right-hand post. 

Igor Matanovic doubled the host's lead six minutes later to complete the turnaround, but Matte Smets' 39th-minute strike restored parity in the tie heading into the break. 

But from there, the Bundesliga outfit took control of the contest, with two goals in three minutes from Grifo and Suzuki putting the game beyond their opponents before the hour. 

Maximilian Eggestein then concluded the rout 11 minutes from time, curling the ball into the left corner after being teed up by Suzuki, who had charged through from his own half. 

Freiburg's next opponent, Celta Vigo, was able to overcome a red mist at Groupama Stadium as it beat nine-man Lyon 2-0 to progress from the tie 3-1 on aggregate. 

Moussa Niakhate was sent off in the 19th minute for a poorly timed challenge on Javi Rueda, and Celta were only able to make their man advantage count in the 61st minute. 

Hugo Alvarez's cross was missed by Ferran Jutgla, but Rueda was on hand to tuck home from inside the six-yard box, with Celta making sure of the win in stoppage time.

After racing in behind the Lyon defence, Jutgla stayed composed before slotting past Dominik Greif, with the hosts' misery compounded in the 96th minute when Nicolas Tagliafico was shown his second yellow card for a reckless foul. 

Real Betis also overcame a first-leg deficit in some style as it beat Panathinaikos 4-0 at Estadio La Cartuja de Sevilla, with Aitor Ruibal starring for the Spaniards. 

Ruibal opened the scoring in the eighth minute before Sofyan Amrabat doubled Betis' lead before the break, as strikes from Cucho Hernandez and Antony sealed the victory in the second half. 

Porto also cruised into the quarter-finals with a 2-0 win over Stuttgart as William Gomes and Victor Froholdt clinched a 4-1 win on aggregate and a date with Nottingham Forest. 

Freiburg's only previous game in major European competition against a Belgian side saw it lose 1-0 in the first leg of this tie, but it produced a considerably better showing here to reach new ground in the Europa League. 

It was helped by the brilliance of its attack but in particularly Suzuki, who finished with team-high totals for shots, touches in the opposition box, chances created, passes in the final third, successful dribbles and duels won.