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| H | Envigado FC | - | Atlético Bucaramanga | 0:0 (0:0) | ||
| R | Atlético Bucaramanga | - | Envigado FC | 3:0 (3:0) | ||
| H: 30.03.2022 21:00 | R: 08.04.2022 02:30 | Sieger: Atlético Bucaramanga | ||||
| H | Unión Magdalena | - | Real Santander | 3:1 (2:1) | ||
| R | Real Santander | - | Unión Magdalena | 1:5 (0:4) | ||
| H: 30.03.2022 22:00 | R: 06.04.2022 21:00 | Sieger: Unión Magdalena | ||||
| H | Cortuluá | - | Fortaleza FC | 0:1 (0:1) | ||
| R | Fortaleza FC | - | Cortuluá | 1:0 (0:0) | ||
| H: 30.03.2022 22:30 | R: 07.04.2022 22:00 | Sieger: Fortaleza FC | ||||
| H | Patriotas FC | - | Tigres FC | 0:0 (0:0) | ||
| R | Tigres FC | - | Patriotas FC | 1:0 (1:0) | ||
| H: 30.03.2022 23:00 | R: 06.04.2022 22:00 | Sieger: Tigres FC | ||||
| H | Alianza Petrolera | - | Jaguares de Córdoba | 1:1 (0:1) | ||
| R | Jaguares de Córdoba | - | Alianza Petrolera | 2:1 (1:1) | ||
| H: 31.03.2022 01:00 | R: 07.04.2022 00:30 | Sieger: Jaguares de Córdoba | ||||
| H | Once Caldas | - | Deportes Quindío | 0:0 (0:0) | ||
| R | Deportes Quindío | - | Once Caldas | 0:1 (0:0) | ||
| H: 01.04.2022 01:00 | R: 08.04.2022 00:30 | Sieger: Once Caldas | ||||
| H | Deportivo Pasto | - | Santa Fe | 0:1 (0:0) | ||
| R | Santa Fe | - | Deportivo Pasto | 3:0 (1:0) | ||
| H: 01.04.2022 03:00 | R: 08.04.2022 03:00 | Sieger: Santa Fe | ||||
| H | Águilas Doradas | - | Deportivo Pereira | 0:1 (0:0) | ||
| R | Deportivo Pereira | - | Águilas Doradas | 4:3 (1:0, 1:2, 1:2) i.E. | ||
| H: 07.04.2022 03:00 | R: 15.04.2022 02:30 | Sieger: Deportivo Pereira | ||||
