The concept of biorefinery constitutes a significant contributing factor to the emerging transition towards a sustainable bioeconomy. In such a context, replacing oil and petrochemicals by biomass may involve several feedstocks, platforms, processes, technologies, as well as final products. This paper concentrates in the complex process of transferring the concept of biorefinery from laboratory to industry, and sheds light on the techno-economic, and complexity management dimensions involved in this endeavor. Towards this end, adopting a systems perspective, the paper presents a structured and comprehensive framework, comprising of the definition of the transformation process, business model development, technoeconomic assessment and strategic positioning and viability assessment, which may be employed to facilitate the engineering at-large and launch of a biorefining venture in a circular bioeconomy context. The framework is applied in the context of a biorefinery plant in a specific region in Southern Greece, which is based on the valorisation of olive mill wastewater (a ‘strong’ and quite common industrial waste in Mediterranean Basin), and produces biopolymers (PHAs) and bioenergy (H2).