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This paper presents a novel design of a stand-alone refrigeration system consisting of a combined organic Rankine cycle and a cascade refrigeration system (ORC-CRS) for low-evaporation-temperature applications (from -55 degrees C to -30 degrees C). Natural refrigerants were used as working fluids: toluene for the organic Rankine cycle and NH3/CO2 for the cascade refrigeration system. A parametric study and a regression analysis have been performed to characterize the system and to estimate the overall system coefficient of performance (COPoval) and exergetic efficiency (etaex_oval). The highest values of COPoval and etaex_oval calculated were 0.79 and 31.6%, corresponding to ORC evaporation temperatures of 315 degrees C and 255 degrees C, respectively. Renewable thermal energy sources from 100 to 350 degrees C can be used to drive the facility, thus reducing dependence on fossil fuel and CO2 emissions. This stand-alone facility seems to be a feasible option to exploit low- and medium-grade thermal energy (geothermal, solar, waste heat) in places where the electricity supply is unreliable.