In the realm of flow boiling research, open microchannels heat sink is garnering more attention due to its potential in enhancing heat transfer and mitigating flow instability. Nevertheless, growing heat dissipation needs necessitate further enhancement of the heat removing capability of flow boiling within open microchannels. In this paper, experimental research on flow boiling in open microchannels utilized a new environmentally friendly refrigerant SF-33 and presented a novel heat transfer enhancement strategy, specifically, a multi-region enhancement strategy for diverse flow pattern stages. A copper heat sink with 25 open microchannels was fabricated, and a layer of copper powder particles was sintered on the channel bottom to create a microporous structured surface in about 1/3 of the inlet region. Several layers of copper wire mesh with micropores were sintered in about 1/3 of the outlet region, and the nanostructures were grown on the wire mesh by chemical treatment, resulting in a micro-nanocomposite structure. The final product formed the multi-stage enhanced open microchannels (MSEOM). The heat transfer performance and pressure drop of SF-33 saturated flow boiling in MSEOM under different operating conditions were determined, and the transitions of flow patterns were visualized to analyze the mechanism of two-phase heat transfer. The study demonstrated that despite SF-33 having a low latent heat of vaporization, its flow boiling heat transfer coefficient in MSEOM was high. This was attributed to the enhanced effect of multi-region surface modifications on heat transfer. Additionally, a vapor plug breakup-dispersed bubble flow pattern was observed for the first time, which resulted from the combined influence of the low surface tension property of SF-33 and the boosted nucleate boiling triggered by the micro-nanostructures in the outlet region.