The Italian club began best of Group F after consecutive wins however were behind when Paraguay forward Antonio Sanabria tapped home inside the six-yard territory.
Giovani Lo Celso multiplied the Spanish side's lead in tremendous style, beating previous Liverpool guardian Pepe Reina from 30 yards through the post.
Patrick Cutrone made it 2-1 yet Milan at that point had Samu Castillejo sent off.
Betis lead by one point with three of their six gathering diversions played. Milan are second, two in front of third-set Olympiakos, who grabbed their first win by beating Luxembourg side Dudelange 2-0.
Somewhere else, Lazio expanded their leverage over third-put Marseille in Group H to five points by beating them 3-1 in France.
Be that as it may, Eintracht Frankfurt moved three points clear at the highest point of that gathering with a 2-0 triumph over Apollon Limassol.
Five-time competition champs Sevilla got their second win and moved best of Group J on objective contrast after they whipped Akhisarspor 6-0 and previous pioneers FK Krasnodar lost 2-1 at Standard Liege.
FC Zurich fought against eminent loss to beat Bayer Leverkusen 3-2 and keep up their 100% record in Group An after Karim Bellarabi had scored twice for the guests.
In Group B, Red Bull Salzburg made it three wins from three with a 3-0 triumph over Rosenborg and in Group C, Zenit St Petersburg battled again from an objective down to beat Bordeaux 2-1 at home, in spite of Artyem Dzyuba missing a punishment.
Fenerbahce defeated a 2-0 shortfall to attract at Anderlecht Group D, while Villarreal moved level on focuses with Rangers in Group G with a vehement 5-0 prevail upon Rapid Vienna.
KRC Genk moved best of Group I with an exciting 4-2 prevail upon Besiktas in Turkey, where five objectives were scored in 17 minutes toward the second's end half.