Twenty-three-times Cup winners Athletic Bilbao were dumped out in sensational circumstances by tiny island side SD Formentera, who sneaked a 1-0 win at San Mames with a header by Alvaro Muniz deep in stoppage-time to reach the last 16 for the first time with a 2-1 aggregate victory.
They were joined by fellow third division side Lleida Esportiu who staged an incredible comeback to win 3-2 at Real Sociedad and go through on away goals, also reaching the last 16 for the first time.
Atletico Madrid eased into the next round by winning 3-0 against Elche, going through 4-1 on aggregate, as club favourite Fernando Torres struck twice in the second half to score his first goals at the club's new Wanda Metropolitano stadium.
Barca coach Ernesto Valverde made nine changes against Murcia to the side that drew 1-1 with Valencia in Sunday's top-of-the-table La Liga clash. As in the 3-0 first-leg win, Spanish striker Paco Alcacer opened the scoring for Barca, heading home a pass that ricocheted off a Murcia defender in the 16th minute.
Murcia survived without conceding for the rest of the half but fell apart in the second. Gerard Pique started and completed a one-two with Aleix Vidal to score the second 11 minutes after the interval and right back Vidal netted with a header.
Denis Suarez added the fourth with a classy touch inside the area to bring a chipped pass under control which he followed with a deft finish into the far corner and reserve team player Jose Arnaiz completed the scoring.
Elsewhere, Sevilla thrashed Cartegena 4-0 to win 7-0 on aggregate while Las Palmas made it through 6-4 on aggregate despite losing 3-2 at home to Deportivo La Coruna.
(Reporting by Richard Martin, editing by Ed Osmond)
