US district judge Vince Chhabria had expressed concerns about a $1.25 billion agreement proposed nearly a year ago, forcing the German giant to take another look at the plan.
Chhabria on Wednesday rejected the latest version of the agreement, stating in a written ruling that it could not be salvaged by "mere tweaks."
"The settlement proposed by these attorneys would accomplish a lot for (Bayer-owned) Monsanto," Chhabria said in the ruling.
"It would accomplish far less for the Roundup users who have not been diagnosed with NHL (Non-Hodgkin Lymphoma) -- and not nearly as much as the attorneys pushing this deal contend."
The agreement would apply to Roundup users already diagnosed with NHL but who have yet to sue the company, as well as anyone who used the weed killer before February of this year but have yet to be diagnosed with the illness.
It included a settlement fund designed to last about four years, while expert testimony in court indicated that it typically takes a decade or more after exposure for the disease to develop, the judge noted in the ruling.
"Bayer is a massive, wealthy company, and it continues to make money specifically from Roundup sales," Chhabria said.
The ruling came just weeks after a federal appeals court in San Francisco upheld a $25 million damages award in a Roundup cancer trial there.
The three-judge panel affirmed the district court's judgment in favor of Edwin Hardeman, who blamed the chemical in Roundup for causing his NHL.
The ruling found the district court properly denied Monsanto's appeal "because evidence showed the carcinogenic risk of glyphosate was knowable at the time of Hardeman's exposure."
A jury originally ordered the company to pay $75 million but a judge later reduced that amount.
The ruling said the award was "at the outer limits of constitutional propriety" but was acceptable, "considering the evidence of Monsanto's reprehensibility."
Hardeman said he used Roundup extensively on his land in Sonoma County -- north of San Francisco -- from the 1980s until 2012.
He filed a complaint against Monsanto in early 2016, a year after being diagnosed with cancer.
The case was considered a "bellwether" in the litigation against Monsanto.
Bayer, an agrochemicals and drugs giant, has been plagued by legal woes since it bought Monsanto in 2018.
Bayer, which is not admitting any wrongdoing, maintains that scientific studies and regulatory approvals show Roundup's main ingredient glyphosate is safe.