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| 1st(1st leg) | Valledupar FC | - | Atlético FC | 1:1 (1:1) | ||
| 2nd (2nd leg) | Atlético FC | - | Valledupar FC | 3:4 (0:0, 0:0, 0:0) pso | ||
| 1st(1st leg): 09/02/2022 19:00 | 2nd (2nd leg): 23/02/2022 19:00 | Winner: Valledupar FC | ||||
| 1st(1st leg) | Real Santander | - | Barranquilla FC | 3:0 (2:0) | ||
| 2nd (2nd leg) | Barranquilla FC | - | Real Santander | 0:0 (0:0) | ||
| 1st(1st leg): 09/02/2022 19:10 | 2nd (2nd leg): 23/02/2022 21:00 | Winner: Real Santander | ||||
| 1st(1st leg) | Boca Juniors de Cali | - | Fortaleza FC | 0:1 (0:0) | ||
| 2nd (2nd leg) | Fortaleza FC | - | Boca Juniors de Cali | 1:0 (1:0) | ||
| 1st(1st leg): 09/02/2022 20:00 | 2nd (2nd leg): 23/02/2022 22:00 | Winner: Fortaleza FC | ||||
| 1st(1st leg) | Tigres FC | - | Leones FC | 2:0 (0:0) | ||
| 2nd (2nd leg) | Leones FC | - | Tigres FC | 1:1 (0:0) | ||
| 1st(1st leg): 09/02/2022 22:30 | 2nd (2nd leg): 23/02/2022 20:00 | Winner: Tigres FC | ||||
| 1st(1st leg) | Orsomarso SC | - | Llaneros FC | 0:0 (0:0) | ||
| 2nd (2nd leg) | Llaneros FC | - | Orsomarso SC | 2:0 (0:0) | ||
| 1st(1st leg): 10/02/2022 20:00 | 2nd (2nd leg): 23/02/2022 20:00 | Winner: Llaneros FC | ||||
| 1st(1st leg) | Deportes Quindío | - | Bogotá FC | 1:0 (0:0) | ||
| 2nd (2nd leg) | Bogotá FC | - | Deportes Quindío | 2:2 (1:1) | ||
| 1st(1st leg): 10/02/2022 23:00 | 2nd (2nd leg): 24/02/2022 22:30 | Winner: Deportes Quindío | ||||
| 1st(1st leg) | Atlético Huila | - | Real Cartagena | 1:0 (0:0) | ||
| 2nd (2nd leg) | Real Cartagena | - | Atlético Huila | 0:0 (0:0) | ||
| 1st(1st leg): 11/02/2022 01:00 | 2nd (2nd leg): 25/02/2022 01:00 | Winner: Atlético Huila | ||||
