| 16. Round | 30/01/2021 | Deportivo Dongu | - | Club Irapuato | 0:7 | ||||
| 17. Round | 05/02/2021 | Club Irapuato | - | Aguacateros CDU | 1:3 | ||||
| 18. Round | 12/02/2021 | Pioneros de Cancún | - | Club Irapuato | 0:3 |  |
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| 19. Round | 19/02/2021 | Club Irapuato | - | Cafessa Jalisco | 0:0 | ||||
| 20. Round | 01/03/2021 | Cafetaleros de Chiapas | - | Club Irapuato | 0:0 | ||||
| 22. Round | 14/03/2021 | Azores de Hidalgo | - | Club Irapuato | 1:4 | |
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| 15. Round | 17/03/2021 | Club Irapuato | - | CD Cuautla | 2:1 | ||||
| 24. Round | 26/03/2021 | Club Irapuato | - | Inter Playa | 1:0 | ||||
| 25. Round | 03/04/2021 | Club de Ciervos | - | Club Irapuato | 0:3 | |
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| 26. Round | 09/04/2021 | Club Irapuato | - | Cañoneros Marina | 6:0 | |
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Colombia