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| 1st(1st leg) | Envigado FC | - | Atlético Bucaramanga | 0:0 (0:0) | ||
| 2nd (2nd leg) | Atlético Bucaramanga | - | Envigado FC | 3:0 (3:0) | ||
| 1st(1st leg): 30/03/2022 20:00 | 2nd (2nd leg): 08/04/2022 01:30 | Winner: Atlético Bucaramanga | ||||
| 1st(1st leg) | Unión Magdalena | - | Real Santander | 3:1 (2:1) | ||
| 2nd (2nd leg) | Real Santander | - | Unión Magdalena | 1:5 (0:4) | ||
| 1st(1st leg): 30/03/2022 21:00 | 2nd (2nd leg): 06/04/2022 20:00 | Winner: Unión Magdalena | ||||
| 1st(1st leg) | Cortuluá | - | Fortaleza FC | 0:1 (0:1) | ||
| 2nd (2nd leg) | Fortaleza FC | - | Cortuluá | 1:0 (0:0) | ||
| 1st(1st leg): 30/03/2022 21:30 | 2nd (2nd leg): 07/04/2022 21:00 | Winner: Fortaleza FC | ||||
| 1st(1st leg) | Patriotas FC | - | Tigres FC | 0:0 (0:0) | ||
| 2nd (2nd leg) | Tigres FC | - | Patriotas FC | 1:0 (1:0) | ||
| 1st(1st leg): 30/03/2022 22:00 | 2nd (2nd leg): 06/04/2022 21:00 | Winner: Tigres FC | ||||
| 1st(1st leg) | Alianza Petrolera | - | Jaguares de Córdoba | 1:1 (0:1) | ||
| 2nd (2nd leg) | Jaguares de Córdoba | - | Alianza Petrolera | 2:1 (1:1) | ||
| 1st(1st leg): 31/03/2022 00:00 | 2nd (2nd leg): 06/04/2022 23:30 | Winner: Jaguares de Córdoba | ||||
| 1st(1st leg) | Once Caldas | - | Deportes Quindío | 0:0 (0:0) | ||
| 2nd (2nd leg) | Deportes Quindío | - | Once Caldas | 0:1 (0:0) | ||
| 1st(1st leg): 01/04/2022 00:00 | 2nd (2nd leg): 07/04/2022 23:30 | Winner: Once Caldas | ||||
| 1st(1st leg) | Deportivo Pasto | - | Santa Fe | 0:1 (0:0) | ||
| 2nd (2nd leg) | Santa Fe | - | Deportivo Pasto | 3:0 (1:0) | ||
| 1st(1st leg): 01/04/2022 02:00 | 2nd (2nd leg): 08/04/2022 02:00 | Winner: Santa Fe | ||||
| 1st(1st leg) | Águilas Doradas | - | Deportivo Pereira | 0:1 (0:0) | ||
| 2nd (2nd leg) | Deportivo Pereira | - | Águilas Doradas | 4:3 (1:0, 1:2, 1:2) pso | ||
| 1st(1st leg): 07/04/2022 02:00 | 2nd (2nd leg): 15/04/2022 01:30 | Winner: Deportivo Pereira | ||||
