Napoli crashed of the Europa League after failing to overcome a two-goal first-leg deficit against Granada.
Piotr Zielinski found the back of the net after just three minutes to provide the hosts with the perfect start at the Stadio Diego Armando Maradona.
But Angel Montoro restored surprise package Granada’s two-goal advantage midway through the opening half of Thursday’s second leg.
Fabian Ruiz put Napoli back in front on the evening shortly before the hour mark, but the LaLiga side held their nerve to take a 3-2 aggregate win and progress to the last 16.
Dutch giants Ajax booked their spot in the next stage following a 2-1 victory against Lille.
Ajax triumphed by the same score in last week’s opening rubber and Davy Klaassen’s goal after 15 minutes provided Lille with an uphill task.
Yusuf Yazici netted from the penalty spot after 75 minutes to draw the French side level on the evening, but David Neres scored in the final minutes as Ajax closed out the tie.
Gerard Moreno’s brace saw Villarreal cruise to a 4-1 aggregate win over Red Bull Salzburg.
Mergim Berisha gave the Austrian visitors hope with his first-half strike to reduce the deficit to just one goal.
But Moreno scored five minutes from the interval before sealing the last-32 clash with a penalty in the closing stages.
Elsewhere, Molde and Shakhtar Donetsk also moved into the next round with comfortable aggregate wins over Hoffenheim and Maccabi Tel-Aviv respectively.