Moving from fossil‐based economies to bio‐based economies is one of humanity's most important necessities. Bio‐based economies are sustainable alternative ways to obtain chemicals, materials, and energy, and biorefineries have been proposed as promising technological schemes for this purpose. However, the economic performance of biorefineries is strongly related to the scale of the process, as different elements (energy consumption, equipment cost, etc.) vary to different degrees when the scale varies. This situation shows the importance of evaluating the performance of the biorefinery at different scales (analysis of scale) from the design stages. The problem with the analysis of these scales is that there is no unanimous definition of ‘scale’ and the term is used imprecisely to refer to the raw material or product. Taking this into consideration, this work proposed a strategy for determining the Minimum Processing Scale for Economic Feasibility (MPSEF) and identifying the minimum scale at which a given biorefinery can operate. As study cases, three different biorefineries, based on different raw materials (cocoyam, Andes berry, and coffee cut stems) were used to exemplify the applicability of the design strategy. The MPSEF calculated for Andes berry, coffee cut stems, and cocoyam‐based biorefineries were 9.27, 35.6 and 683 ton day−1, respectively. These results showed the application of the design strategy and how it allows the determination of the minimum amount of feedstock to be processed to achieve a positive economic performance, and from this point, to calculate the rate of return that an investor would require and the appropriate scale to achieve it. © 2018 Society of Chemical Industry and John Wiley & Sons, Ltd