Antoine Griezmann scored one and set up another but could not prevent Atletico Madrid tumbling out of the Copa del Rey as Girona progressed on away goals after a thrilling 3-3 draw.
Real Madrid and Sevilla each avoided upsets on Wednesday, their first-leg victories proving enough despite losses to Leganes and Athletic Bilbao respectively.
Defeat for Real, however, means they have now won only two of their five matches this year while Santiago Solari's frosty relationship with Isco shows no signs of improvement.
Isco started, but struggled, and was replaced in the 68th minute.
For Atletico, Griezmann came off the bench in the second half and turned the tie in their favour on Wednesday, teeing up Angel Correa and then scoring himself to give his team a 3-2 lead at a rocking Wanda Metropolitano.
But Girona pulled out one more surprise to go through to the quarter-finals as Seydou Doumbia's shot found the corner in the 88th minute, snatching a 4-4 draw on aggregate after last week's first leg finished 1-1.
Griezmann had scored then too, and in between against Levante on Saturday. This was his eighth goal in as many matches.
"We thought we could leave Griezmann on the bench and only throw him on in the second half to do what he did, score the goal for 3-2,"
Atletico coach Diego Simeone said. "I didn't take into account Girona scoring again."
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