Two-phase flow operational stability of refrigerants R245fa, R236fa, and R1234ze(E) in 100 x 100 μm2 multi-microchannels for cooling of future high-performance 3D stacked architectures with interlayer cooling has been addressed in the current experimental investigation. Without any inlet restrictions in the micro-evaporator, significant flow instabilities, back flow, and flow maldistribution led to high-amplitude and high-frequency temperature and pressure oscillations. Such undesired phenomena were inhibited by placing rectangular restrictions (micro-orifices) at the inlet of each channel, thus ensuring a wide range of stable two-phase flow operating conditions. The effects of different orifice expansion ratios and fluids on the performance of the evaporator were studied by using suitably designed modular test sections. Simultaneous high-speed video and infra-red camera visualizations of the two-phase flow and heat transfer dynamics across the micro-evaporator area allowed the various different operating regimes to be identified and then represented by the two-phase flow operational maps. Two-phase flow flashed by the micro-orifices was identified as the optimal operating condition, while dissipating high heat fluxes and keeping the junction chip temperature below a typical CPU operating condition. In the present study, a novel in-situ pixel by pixel technique was developed to calibrate the raw infra-red images, thus converting them into two-dimensional temperature fields of 10’000 pixels over the test section surface. A comprehensive analysis of those temperature maps supported by the flow visualization videos confirmed that the two-phase flow patterns appearing in the channel and the transitions between them have a remarkable influence on the heat transfer coefficients, which were determined taking into account 3D heat spreading. The inlet and the outlet restriction pressure losses were quantified in order to accurately simulate the hydraulic performance of microchannel evaporators and provide more reliable heat transfer data. The heat transfer coefficients were determined with a very fine resolution that enabled the trends in the heat transfer coefficients along the channel length in the neighborhood of the flow transition from coalescing bubble to the annular flow to be studied in detail. It was shown that the heat transfer coefficient does not change sharply at the transition zone, but rather has a smooth change in trend. The characteristic U-shape of the heat transfer coefficient trend was observed, where the descending branch of the curve corresponds to the coalescing elongated bubble flow regime, while ascending one represents the increasing heat transfer coefficient in the annular flow regime. A good agreement of the experimental heat transfer coefficients and one existing flow pattern-based prediction method was found and a new vapor quality buffer is proposed as an update of this model.