Heteroepitaxially flexible oxide systems have been intensely developed and considered as the most promising materials for leading the creation of next-generation flexible electronic devices. Among them, perovskite manganites have attracted significant attention with their abundant and novel properties such as colossal magnetoresistance (CMR) and metal-insulator transition. However, the requirement of high quality samples hampers this field, not to mention the advanced nanoengineering. In this study, fluorophlogopite mica (F-mica) is selected as a flexible substrate to fabricate heteroepitaxial Pr0.5Ca0.5MnO3 (PCMO) with a nanocolumn structure. Through a precise control of thickness, different morphologies are realized to manipulate the magnetotransport properties (reduction of melting field). Moreover, thanks to the excellent flexibility of F-mica, mechanical modulation of CMR (≈1000%) can be achieved in different flex modes while the magnetic properties remain unaffected. Detailed bending tests are performed to study the behavior of resistive change (≈30%). Through the combination of high flexibility, high quality PCMO, and well-designed nanocolumn structure, the study exhibits the significant controllability of CMR via mechanical bending, and manifests the potential of such a heteroepitaxially flexible oxide system which can be applied on flexible magnetoresistive devices and sensors.